Novel Anticancer Strategies

Bousbaa, Hassan

doi:10.3390/pharmaceutics13020275

Cited by 11 publications

(9 citation statements)

References 16 publications

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“…3D cell cultures have been widely used due to their capacity to reproduce the in vivo tumor microenvironment, including oxygen and nutrient gradients, cell heterogeneity, gene expression, and cell-to-cell and cell-to-extracellular matrix interactions [32,52]. To validate the findings observed in 2D monolayer cell cultures, 3D models were used as an alternative to recapitulate the real tumor.…”

Section: Discussionmentioning

confidence: 99%

Navitoclax Enhances the Therapeutic Effects of PLK1 Targeting on Lung Cancer Cells in 2D and 3D Culture Systems

et al. 2022

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The efficacy of antimitotics is limited by slippage, whereby treated cells arrested in mitosis exit mitosis without cell division and, eventually, escape apoptosis, constituting a serious resistance mechanism to antimitotics. Strategies to overcome slippage should potentiate the cancer cell killing activity of these antimitotics. Such strategies should accelerate cell death in mitosis before slippage. Here, we undertook a mechanistic analysis to test whether the apoptosis activator Navitoclax potentiates apoptosis triggered by the antimitotic BI2536, a potent inhibitor of Polo-like kinase 1 (PLK1) with the goal of overcoming slippage. We found that cancer cells in 2D cultures treated with BI2536 alone accumulate in mitosis, but a significant fraction of arrested cells undergo slippage and survive. Remarkably, combining BI2536 with Navitoclax dramatically reduces slippage, shifting the cell fate to accelerated death in mitosis. The results are confirmed in 3D spheroids, a preclinical system that mimics in vivo tumor drug responses. Importantly, in 3D spheroids, the effect of the BI2536/Navitoclax combination requires a lower therapeutic dosage of each drug, underlying its potential to improve the therapeutic index. Our results highlight the relevance of apoptosis potentiators to circumvent slippage associated with antimitotics. The combination of BI2536 with Navitoclax shows in vitro synergy/additive effect, which warrants further clinical research.

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Section: Discussionmentioning

confidence: 99%

Navitoclax Enhances the Therapeutic Effects of PLK1 Targeting on Lung Cancer Cells in 2D and 3D Culture Systems

et al. 2022

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“…Cancer immunotherapy (IT) is a novel approach to CRC therapy (Table 1). It uses medicines (immune checkpoint inhibitors) to improve the ability of a person's immune system to better recognise and destroy cancer cells [6]. Immunotherapy can be used to treat patients with advanced colorectal cancer.…”

Section: Current Therapeutic Approaches For Crcmentioning

confidence: 99%

“…Among those confines is the poor solubility of the drug in an aqueous solution, drug resistance, non-specific targeting, low-retention effectiveness, and adverse effects on normal cells. Therefore, novel therapeutic strategies are constantly needed to improve the safety and effectiveness of cancer therapy and overcome its drawbacks [6].…”

Section: Introductionmentioning

confidence: 99%

Promising Therapeutic Strategies for Colorectal Cancer Treatment Based on Nanomaterials

Krasteva

Georgieva

2022

Pharmaceutics

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Colorectal cancer (CRC) is a global health problem responsible for 10% of all cancer incidences and 9.4% of all cancer deaths worldwide. The number of new cases increases per annum, whereas the lack of effective therapies highlights the need for novel therapeutic approaches. Conventional treatment methods, such as surgery, chemotherapy and radiotherapy, are widely applied in oncology practice. Their therapeutic success is little, and therefore, the search for novel technologies is ongoing. Many efforts have focused recently on the development of safe and efficient cancer nanomedicines. Nanoparticles are among them. They are uniquewith their properties on a nanoscale and hold the potential to exploit intrinsic metabolic differences between cancer and healthy cells. This feature allows them to induce high levels of toxicity in cancer cells with little damage to the surrounding healthy tissues. Graphene oxide is a promising 2D material found to play an important role in cancer treatments through several strategies: direct killing and chemosensitization, drug and gene delivery, and phototherapy. Several new treatment approaches based on nanoparticles, particularly graphene oxide, are currently under research in clinical trials, and some have already been approved. Here, we provide an update on the recent advances in nanomaterials-based CRC-targeted therapy, with special attention to graphene oxide nanomaterials. We summarise the epidemiology, carcinogenesis, stages of the CRCs, and current nanomaterials-based therapeutic approaches for its treatment.

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“…A further goal of this research was to study the potential of the prepared carriers as a drug delivery system dedicated to anthracycline antibiotics. Searching for new compounds that exhibit anticancer properties or might modulate or enhance the activity of known antineoplastic agents is a great challenge and an emerging need in modern medicine. , The abovementioned is especially important in the context of the growing number of cases of cancer as well as increasing multidrug-resistance phenomena. Furthermore, the reduction of nonspecific interaction of chemotherapeutic agents, which usually causes depletion of the quality of patients’ lives, can be considered a good characteristic for the development of new approaches to anticancer treatment …”

Section: Results and Discussionmentioning

confidence: 99%

Membrane-Active Thermoresponsive Block Copolymers Containing a Diacylglycerol-Based Segment: RAFT Synthesis, Doxorubicin Encapsulation, and Evaluation of Cytotoxicity against Breast Cancer Cells

Kurowska,

Markiewicz,

Niemirowicz-Laskowska

et al. 2023

Biomacromolecules

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Herein, we report the formation of drug delivery systems from original thermoresponsive block copolymers containing lipid-based segments. Two acrylate monomers derived from palmitic-or oleic-acid−based diacylglycerols (DAGs) were synthesized and polymerized by the reversible addition−fragmentation chain transfer (RAFT) method. Well-defined DAG-based polymers with targeted molar masses and narrow molar mass distributions were next used as macro-chain transfer agents (macro-CTAs) for the polymerization of N-isopropylacrylamide (NIPAAm) or N-vinylcaprolactam (NVCL). The obtained amphiphilic block copolymers were formed into polymeric nanoparticles (PNPs) with and without encapsulated doxorubicin and characterized. Their biological assessment indicated appropriate cytocompatibility with the representatives of normal cells. Furthermore, compared to the free drug, increased cytotoxicity and apoptosis or necrosis induction in breast cancer cells was documented, including a highly aggressive and invasive triple-negative MDA-MB-231 cell line.

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Novel Anticancer Strategies

Abstract: Cancer incidence and mortality continue to increase rapidly worldwide [...]

Cited by 11 publications

References 16 publications

Navitoclax Enhances the Therapeutic Effects of PLK1 Targeting on Lung Cancer Cells in 2D and 3D Culture Systems

Navitoclax Enhances the Therapeutic Effects of PLK1 Targeting on Lung Cancer Cells in 2D and 3D Culture Systems

Promising Therapeutic Strategies for Colorectal Cancer Treatment Based on Nanomaterials

Membrane-Active Thermoresponsive Block Copolymers Containing a Diacylglycerol-Based Segment: RAFT Synthesis, Doxorubicin Encapsulation, and Evaluation of Cytotoxicity against Breast Cancer Cells

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